Interference with its oxygen supply is the major stress which the fetus encounters in utero. Our aim is to understand the fetal cardiovascular response to such interference, to determine the factors which regulate it, and to assess the circulatory response to hypoxemia with increasing gestational age. Studies by other investigators on the fetal circulation during asphyxia have been done acutely, under anesthesia, and have not separated the effects of hypoxemia from acidemia or full asphyxia. We have been able to examine the cardiovascular respose to hypoxemia in chronic fetal preparations. Fetal and meternal hypoxemia were produced by administering low oxygen gas mixtures to the standing, conscious ewe. Fetal heart rate, arterial pressure, and arterial blood gases were repeatedly measured. Cardiac output, umbilical blood flow, and individual organ blood flows were measured simultaneously at pointsduring the control, hypoxemic, and recovery states, using radionuclide-labelled microspheres. Preliminary observations have been reported for late-gestation fetal lambs. In the proposed studies, fetal and maternal hypoxemia are to be determined by the direct measurement of oxygen contents. We plan to measure changes in cardiovascular function, umbilical blood flow, oxygen consumption, umbilical vascular resistance, and blood flow to all fetal tissues, over a wide range of hypoxemic and recovery states, and mid- and late-gestation fetuses and in neonatal lambs during the first week after birth. We plan to study the respective roles of alpha- and beta-adrenergic and parasympathetic stimulation during hypoxemia, by means of selective pharmacologic blockade. These studies should clarify the pattern of developing autonomic nervous control over the fetal circulation, and will provide a physiologic background from which we may improve our management of intrauterine asphyxia. BIBLIOGRAPHIC REFERENCES: Novy, M.J., Cohn, H.E., Piasecki, G.J., and Jackson, B.T. Fetal hemodynamic changes during graded reductions in uterine blood flow. The physiologist, 18:335, 1975 (abstract).